The objectives of these studies are to clarify the mechanism of the cerebral microcirculatory alterations following experimental percussion-type brain injury in anesthetized cats. This type of brain injury induces pial arteriolar dilation associated with reduced responsiveness to the vasoconstrictor effects of arterial hypocapnia and with reduced ability to dilate in response to arterial hypotension. The vessels which show these abnormalities have lesions in their vascular smooth muscle and discrete destructive lesions in their endothelium. These abnormalities are mediated by free oxygen radicals generated in association with increased prostaglandin synthesis. The proposed experiments will determine the timing of the generation of the free oxygen radicals. They will identify the effects of enzymatically generated free radicals on cerebral arteriolar caliber and responsiveness and on the morphology of these vessels, as well as on the permeability of the blood-brain barrier. Other studies will ascertain the time-course of the pial arteriolar changes following brain injury over a period of 24 to 48 hours after brain injury. The responses of pial arterioles to brain injury will be compared to the responses of cerebellar arterioles to identify whether or not the responses of cerebral microvessels in infratentorial areas differ from those in supratentorial areas. Also, we will examine the role of calcium and of vasoactive intestinal polypeptide in the mediation of the cerebral microcirculatory effects of brain injury.